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Prognostic factors after surgery for locally recurrent rectal cancer: an overview.

PURPOSE: Local recurrence of rectal cancer occurs in a considerable group of patients who have undergone radical treatment for primary tumour. The treatment of choice is surgical resection but the prognosis remains poor, as a negative margin excision is possible in only a small subset of patients. A review of prognostic factors for locally recurrent rectal cancer (LRRC) after surgery is presented. METHODS: We systematically reviewed the literature for reports on prognostic factors after surgical excision of LRRC. These reports were identified through a review of the Medline database from 1982 to 2004. RESULTS: This review highlights the most important prognostic factors for LRRC patients treated with surgery. Data are grouped on the basis of the prognostic factors investigated. CONCLUSIONS: R0 resection seems to be the only reliable prognostic factor; however, symptoms, pre-operative CEA doubling time, performance status and pre-operative radiotherapy can help patient selection before surgery. The results of this review provide the basis for improved outcome, aiming to assess patients who would benefit from reoperation.

Aged↗

Initial high-grade T1 urothelial cell carcinoma: feasibility and prognostic significance of lamina propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-non-treated patients.

OBJECTIVES: This study aimed to determine the prognostic value of depth of lamina propria invasion in initial high-grade T1 bladder tumors. Secondary aims were to evaluate the prognostic significance of concomitant carcinoma in situ (CIS) and the impact of bacillus Calmette-Guérin (BCG) treatment as well as to assess the feasibility of microstaging by pathologists in a community setting. PATIENTS AND METHODS: Ninety-seven tumors were available for study and were substaged according to invasion superficial to, into or beyond the muscularis mucosae (MM) (T1a, T1b, T1c). Outcomes were compared by chi-square analysis. Recurrence-free and progression-free survival estimates were obtained by Kaplan-Meier analysis. BCG treatment impact and prognostic significance of CIS were also evaluated (Cox regression). RESULTS: T1 subclassification was possible in 87% (85/97) of cases: 38 (39.1%) T1a, 10 (10.3%) T1b, and 37 (38.1%) T1c; in 12 patients (12.4%) substaging was not possible. Mean age was 66.4 years and mean follow-up was 53 months. Recurrence rates were similar for all groups. By contrast, the progression rate for deep lamina propria-invasive tumors, i.e. T1b and T1c, was 34% (16/47) in comparison to 8% (3/38) for T1a (p=0.016). Progression-free intervals were significantly different in patients with (T1b, T1c) or without (T1a) deep lamina propria involvement (p=0.003), regardless of BCG treatment (p=0.02). BCG-treated patients (67 cases) showed a slight trend towards a better outcome, but differences were not significant. CIS was associated with more than 50% of cases that progressed. On multivariate analysis, depth of invasion and CIS remained two independent prognostic factors, increasing the hazards ratio of progression to 4.47 and 3.19 respectively. CONCLUSIONS: The depth of invasion in the TURB specimens is an independent prognostic factor for T1 bladder cancer even in BCG-treated patients. Associated CIS significantly increases the risk of progression in these patients. The percentage of cases that can be substaged according to the depth of lamina propria involvement increases over time with the collaboration between urologists and pathologists. Consequently, we support that routine pathological assessment of the level of MM invasion in patients with stage T1 bladder cancer should be included in the histopathological report.

Adjuvants, Immunologic↗

Immunohistochemical expression of Ki-67 antigen, cox-2 and Bax/Bcl-2 in prostate cancer; prognostic value in biopsies and radical prostatectomy specimens.

PURPOSES: To elucidate the prognostic value of the immunohistochemical (IHC) expression of Bcl-2, Bax, Cox-2 and Ki-67 antigen in biopsy cores (C) and surgical specimens (SP) of prostate cancer (PC) and to determine the C to SP reproducibility. MATERIAL AND METHODS: The IHC study was carried out in 91 patients operated by means of radical prostatectomy (RP) with available formalin-fixed paraffin-embedded material from both C and SP. RESULTS: The IHC expression of Bcl-2 in C and SP was very low (5%). Bax was expressed in almost all the patients and did not show any prognostic value. We observed a good reproducibility between C and SP for all molecules except with Bax. In prostate C, Ki-67 and Cox-2 were considered positive in 42.9% and 67% of the patients respectively, and were related to disease-free survival in the univariate analysis. The expression of these two markers in SP was observed in 51.6% and 79.1% of the patients and the expression of Ki-67 in SP maintained its independence as prognostic factor in the multivariate analysis related to disease-free survival. CONCLUSIONS: The IHC expression of Ki-67 and Cox-2 proteins in our study do offer valuable prognostic information, mostly the first one. Thus, we think these markers might be studied in larger series of patients for its further validation as prognostic factors in prostate biopsies.

Aged↗

Prognostic model based on calcium-related genes predicts prognosis and reveals the immune landscape of acute myeloid leukemia.

Acute myeloid leukemia (AML) exhibits heterogeneous outcomes and lacks reliable prognostic markers. As a critical regulator of cell fate, the prognostic value of calcium signaling in AML requires investigation. This study aimed to construct a calcium-related gene (CRG)-based prognostic model for AML. Differential analysis on RNA-seq data was conducted for AML from The Cancer Genome Atlas and Gene Expression Omnibus (GEO). Intersecting differentially expressed genes and CRGs yielded AML-associated differentially expressed CRGs (DECRGs). A prognostic model was developed using univariate/multivariate Cox regression and least absolute shrinkage and selection operator (LASSO) and validated in a GEO dataset. Bioinformatics analyses explored the links between risk groups and immune characteristics, genomic mutations, and drug sensitivity. Key genes' effects on cell proliferation, apoptosis, and differentiation were verified in vitro using CCK-8 assay, colony formation assay, and flow cytometry. The 13-DECRG-based model distinguished high- and low-risk patients in both training and validation cohorts, with high-risk patients showing a worse prognosis. The risk score was an independent prognostic factor. Immune analysis revealed a unique immune microenvironment for the high-risk group. CAMK2A overexpression inhibited cell proliferation and colony-forming ability, promoted cell apoptosis, and induced an increased proportion of CD11b- and CD14-positive cells. In vitro experiments indicated CAMK2A-induced suppression of AML cells' malignant phenotype by activating the P53 signaling pathway. An AML CRG-based model with favorable risk stratification performance was constructed. In vitro experiments revealed CAMK2A-induced inhibition of the malignant phenotype via suppressing proliferation, promoting apoptosis, and facilitating myeloid differentiation in AML cells. This study provides novel evidence for understanding CRGs in AML as well as the potential functions of CAMK2A.

Journal Article↗

The prognostic validity of the ventricular evoked response (VER) signals in cardiac transplantation.

INTRODUCTION: Computerized heart allograft rejection monitoring (CHARM) used for non-invasive rejection monitoring in heart transplant recipients is based on the analysis of ventricular evoked response (VER) signals. The aim of this study was to evaluate the prognostic validity of the Tslew(C), a parameter calculated from the VER. METHODS: During orthotopic heart transplantation, 2 unipolar fractally coated screw-in leads were implanted epimyocardially, one to the left and one to the right ventricle, and connected to a telemetric pacemaker. Recordings of intramyocardial electrograms were performed routinely at the hospital. Data processing was done, artifacts were eliminated, and trend curves of the patients were displayed. Tslew(C) was calculated from the tangent of VER and evaluated from 105 patients. The patients were divided into survivor and non-survivor groups. For statistical analysis, the 2-tailed t-test was performed. RESULTS: Patients in the non-survivors group compared with the control group showed a significantly lower Tslew(C) in the final follow-up (p < 0.001). The differences were even more impressive in patients with recorded intramyocardial electrograms 30 days before death or with a cardiac reason for death. Tests were performed to find an optimal prognostic threshold of the Tslew(C), and the value of 26 mV was finally found. CONCLUSION: Tslew(C) can function as prognostic factor after orthotopic heart transplantation. Further studies should be initiated to provide the prognostic threshold so that patients would not be forced to show up routinely every 4 weeks for follow-up visits. Patients would only have to be admitted to the hospital if the Tslew(C) were less than this prognostic threshold.

Cardiomyopathy, Dilated↗

Comparison of the prognostic value of cardiopulmonary exercise testing between male and female patients with heart failure.

BACKGROUND: Cardiopulmonary exercise testing (CPX) clearly holds prognostic value in the heart failure (HF) population. Studies investigating the prognostic value of CPX in individuals with HF have consistently examined predominantly male groups. The purpose of the present study was to examine the prognostic value of CPX in a female HF group. METHODS: Seventy-five female and 337 male subjects diagnosed with HF participated in this study. The ability of peak oxygen consumption (VO(2)) and the minute ventilation/carbon dioxide production (VE/VCO(2)) slope to predict cardiac-related events were assessed. RESULTS: In the year following CPX, the female group suffered 26 cardiac-related events (8 deaths/18 hospitalizations), while the male group suffered 89 cardiac-related events (20 deaths/69 hospitalizations). The hazard ratios for peak VO(2) and the VE/VCO(2) slope were 4.0 (95% confidence interval: 2.6-6.1, p<0.001) and 4.2 (95% confidence interval: 2.7-6.6, p<0.001) in the male group and 3.8 (95% confidence interval: 1.7-8.5, p<0.001) and 4.3 (95% confidence interval: 1.8-9.8, p<0.001) in the female group. In both the male and female groups, Cox multivariate analysis revealed VE/VCO(2) slope was the strongest predictor of cardiac-related events while peak VO(2) added significant predictive value and was retained in the regression. CONCLUSION: The results of the present study indicate that the prognostic value of peak VO(2) and the VE/VCO(2) slope are similar in men and women diagnosed with HF. In both men and women, the prognostic power of the VE/VCO(2) slope is greater than that of peak VO(2).

Carbon Dioxide↗

The elusive prognostic value of systemic endothelial function in patients with chest pain syndrome.

The prognostic value of systemic endothelial dysfunction still remains uncertain in ischemic heart disease. The aim of the study was to establish the prognostic value of ultrasonically assessed systemic endothelial dysfunction in patients with chest pain syndrome and to assess whether this information was incremental to that already provided by simple parameters derived from echocardiography, such as left ventricular mass index or ejection fraction. One hundred ninety-five in-hospital patients (age=60+/-10 years; 63 females) with known or suspected CAD have been enrolled. All of the patients underwent, on different days, coronary angiography, endothelium-dependent FMD testing of the brachial artery by high-resolution ultrasound and resting 2D-echocardiography evaluation. The result of the FMD has been defined as the percent change in the internal diameter of the brachial artery during reactive hyperemia related to baseline. All patients were followed-up for a median of 27 months. During follow-up there were 17 deaths (9 cardiac), 4 non-fatal myocardial infarction (MI), and 18 late clinically-driven revascularization procedures. By a multivariate analysis, echocardiographically assessed ejection fraction (odds ratio: 2.32; 95% confidence interval: 1.24-4.33; p=0.008) and angiographically assessed CAD (odds ratio: 2.82; 95% confidence interval: 1.40-5.67; p=0.003), were independent prognostic predictors of events. In patients with known or suspected CAD, systemic endothelial dysfunction did not show a significant prognostic value. Echocardiographic indices of structural left ventricular damage appear to have a stronger prognostic value than functional indices of peripheral vascular damage in risk stratifying ischemic patients.

Chest Pain↗

Prognostic value of the VE/VCO2 slope calculated from different time intervals in patients with suspected heart failure.

BACKGROUND: Maximal exercises testing, whether involving cycling- or walking-based protocols, are often not well tolerated in patients with chronic heart failure (CHF). The peak oxygen consumption and the slope of the relation between ventilation (V(E)) and carbon dioxide production (V(CO(2))) are independent predictors of outcome and help risk stratification. The prognostic usefulness of submaximal exercise testing is not clear. The aim of the present study was to assess the prognostic value of the V(E)/V(CO(2)) slope when derived from data acquired from submaximal exercise. METHODS: 394 patients referred with breathlessness and suspected heart failure (74% male) (mean+/-S.D.) age 60+/-12 years; BMI 27+/-5 performed a CPET to determine peak V(O(2)) and the V(E)/V(CO(2)) slope. The V(E)/V(CO(2)) slope was calculated using least squares regression from data acquired from the first 25% of exercise (mean V(E)/V(CO(2)) slope+/-SD; 30.6+/-5.7), 50% (29.6+/-6.9), below the ventilatory compensation point (sub-VCP) (29.9+/-6.8), and all data points (full slope) (32.1+/-7.8). For each measure, patients were divided into quartiles and Kaplan-Meier curves were constructed to determine probability of death after 24 months. The prognostic value of the different classifications was assessed using the chi(2) statistic from the Mantel-Cox log-rank test. RESULTS: During a mean follow-up period of 41+/-19 months, 48 patients died. For the V(E)/V(CO(2)) slope, the log-rank statistic was greatest for the full slope (chi(2)=53.7; P=0.0001), followed by the sub-VCP (chi(2)=45.5; P=0.0001), 50% (chi(2)=41.9; P=0.0001), and 25% (chi(2)= 26.0; P=0.01). The pair-wise log-rank statistic between the fourth and third quartiles was also greatest using the full slope (chi(2)=25.4; P=0.001) followed in order by the sub-VCP (chi(2)=20.1; P=0.001), 50% (chi(2)=19.7; P=0.001), and 25% (chi(2)=14.2; P=0.05). Using the stratified slope measurements entered into a Cox regression analysis using a forward LR stepwise elimination procedure; only the full slope remained significant (P=0.0001). CONCLUSIONS: The V(E)/V(CO(2)) slope should be calculated from all data points to optimise prognostic sensitivity. Data acquired from the first 50% of exercise and below the VCP provide adequate prognostic surrogates in patients who may not be able to perform maximal exercise testing (i.e. in patients with a respiratory exchange ratio<1.10).

Aged↗

Coexpression of cyclooxygenase-2 and thymidine phosphorylase as a prognostic indicator in patients with FIGO stage IIB squamous cell carcinoma of uterine cervix treated with radiotherapy and concurrent chemotherapy.

PURPOSE: To evaluate the prognostic significance of thymidine phosphorylase (TP) and coexpression of cyclooxygenase-2 (COX-2)/TP, and to investigate the relationship between COX-2 and TP expression in squamous cell carcinoma of the uterine cervix. METHODS AND MATERIALS: Cancer specimens from 75 patients with International Federation of Gynecology and Obstetrics Stage IIB squamous cell carcinoma of the uterine cervix who had undergone radiotherapy and concurrent chemotherapy were immunohistochemically stained with COX-2 and TP antibodies and scored. The prognostic significance of their expression status, and the relationship between COX-2 and TP was investigated. RESULTS: TP predominantly stained cytoplasm and the cell membrane of the tumor cells mainly in a diffuse and intense manner. TP was negative (<10% distribution) in 17%, 1+ (10-50%) in 25%, and 2+ (>50%) in 57% of patients. TP overexpression was related to a marginal prognostic significance of a poor 5-year overall survival (p = 0.082, log-rank test) and a high locoregional recurrence rate (p < 0.1, chi-square test). COX-2 and TP coexpression was observed in 24% of patients and was significantly related to poor 5-year disease-free and overall survival rates (p = 0.0083 and p = 0.025, respectively), a high pelvic lymph node involvement rate, a poor response to treatment, and a greater incidence of locoregional recurrence (p < 0.05). By multivariate analyses, only COX-2, TP, and coexpression of COX-2/TP were significant independent prognostic indicators of patient survival. All tumors showed 1+ or 2+ TP expression when COX-2 was positive, and no tumor expressed COX-2 when TP was negative (p = 0.03). In contrast, 77% of tumors expressed 1+ or 2+ TP without the synchronous expression of COX-2. CONCLUSIONS: Thymidine phosphorylase expression or COX-2/TP coexpression may be used as a molecular prognostic marker for squamous cell carcinoma of the uterine cervix. TP appears to be an important downstream molecule of COX-2 during angiogenesis and may be a new target for the treatment of uterine cervical cancer.

Carcinoma, Squamous Cell↗

Oxygen-modifying treatment with ARCON reduces the prognostic significance of hemoglobin in squamous cell carcinoma of the head and neck.

PURPOSE: To evaluate the prognostic significance of hemoglobin (Hb) levels measured before and during treatment with accelerated radiotherapy with carbogen and nicotinamide (ARCON). METHODS AND MATERIALS: Two hundred fifteen patients with locally advanced tumors of the head and neck were included in a phase II trial of ARCON. This treatment regimen combines accelerated radiotherapy for reduction of repopulation with carbogen breathing and nicotinamide to reduce hypoxia. In these patients, Hb levels were measured before, during, and after radiotherapy. RESULTS: Preirradiation and postirradiation Hb levels were available for 206 and 195 patients respectively. Hb levels below normal were most frequently seen among patients with T4 (p < 0.001) and N2 (p < 0.01) disease. Patients with a larynx tumor had significantly higher Hb levels (p < 0.01) than other tumor sites. During radiotherapy, 69 patients experienced a decrease in Hb level. In a multivariate analysis there was no prognostic impact of Hb level on locoregional control, disease-free survival, and overall survival. Primary tumor site was independently prognostic for locoregional control (p = 0.018), and gender was the only prognostic factor for disease-free and overall survival (p < 0.05). High locoregional control rates were obtained for tumors of the larynx (77%) and oropharynx (72%). CONCLUSION: Hemoglobin level was not found to be of prognostic significance for outcome in patients with squamous cell carcinoma of the head and neck after oxygen-modifying treatment with ARCON.

Administration, Inhalation↗

Epidermal growth factor receptor as a prognostic factor in locally advanced rectal-cancer patients treated with preoperative chemoradiation.

PURPOSE: We investigated the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer treated with preoperative chemoradiation. METHODS AND MATERIALS: Pretreatment biopsy specimens from 92 patients with locally advanced rectal cancer were examined for EGFR expression by immunohistochemistry. EGFR expression was assessed by immunoreactive score (IRS). The prognostic value of EGFR expression was evaluated according to the level of EGFR expression. RESULTS: Epidermal growth factor receptor expression was positive in 65 patients (71%). EGFR expression levels were low (IRS 0 to 5) in 83 patients (90%) and high (IRS 6 to 7) in 9 patients (10%). A high level of EGFR expression was statistically significant for shorter overall survival (p = 0.013), disease-free survival (p = 0.002), and distant metastasis-free survival (p = 0.003), as compared with a low level of expression in univariate analysis. Grouping based on positive or negative EGFR expression did not represent prognostic significance for survival. In multivariate analysis, high EGFR expression was an independent prognostic factor for decreased disease-free survival (relative risk 2.4, p = 0.041) and distant metastasis-free survival (relative risk 2.6, p = 0.04). CONCLUSIONS: Our results suggest that high level of EGFR expression in a pretreatment biopsy specimen may be a significant adverse prognostic factor for disease-free survival and distant metastasis-free survival.

Aged↗

A prognostic scoring system for locoregional control in nasopharyngeal carcinoma following conformal radiotherapy.

PURPOSE: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy. METHODS AND MATERIALS: Patients with nondisseminated NPC at initial presentation (n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control. RESULTS: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic WHO type I-II, serum LDH level > or =410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%. CONCLUSION: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.

Adult↗

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: results of study CAO/ARO/AIO-94.

PURPOSE: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. METHODS AND MATERIALS: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. RESULTS: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% +/- 7.8%; inadequate RT, 21.2% +/- 5.6%; adequate RT, 6.8% +/- 1.4%; p = 0.0001) and DFS (no RT, 55.1% +/- 9.1%; inadequate RT, 57.4% +/- 6.3%; adequate RT, 69.1% +/- 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. CONCLUSION: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.

Aged↗

The prognostic importance of left ventricular outflow obstruction in hypertrophic cardiomyopathy varies in relation to the severity of symptoms.

OBJECTIVES: The aim of this study was to investigate whether the prognostic importance of left ventricular (LV) outflow obstruction in hypertrophic cardiomyopathy (HCM) is influenced by other predictors of morbidity and mortality. BACKGROUND: It remains unknown whether the effect of outflow obstruction on clinical outcome in HCM is influenced by other determinants of survival. METHODS: We assessed the impact of severity of symptoms, LV wall thickness, atrial fibrillation, and age on the prognostic importance of outflow obstruction in a large HCM population. RESULTS: Of 526 consecutive HCM patients, 141 (27%) had outflow obstruction. During a follow-up of 4.5 +/- 4.1 years, 34 patients died of HCM. The incidence of cardiovascular death was significantly higher among patients with LV obstruction than among those without obstruction (relative risk [RR] = 2.14; p = 0.02). The prognostic power of the outflow gradient changed in relation to severity of symptoms (p = 0.024). At initial evaluation, LV obstruction was a significant predictor of cardiovascular mortality only in New York Heart Association (NYHA) functional class I to II patients (hazard ratio [HR] = 2.38; p = 0.025). During follow-up, at time of development of severe symptoms, the outflow gradient lost its prognostic significance (HR = 1.18; p = 0.66), whereas NYHA functional class III to IV was associated with an eight-fold increase in risk of cardiovascular mortality (HR = 7.90; p < 0.001). CONCLUSIONS: In patients with HCM, the prognostic importance of LV outflow obstruction varies in relation to the severity of symptoms. In patients with mild or no symptoms, obstruction is an important predictor of cardiovascular death. After development of severe symptoms, NYHA functional class becomes the dominant marker of prognosis independently of the presence of an outflow gradient.

Cardiomyopathy, Hypertrophic↗

Cardiopulmonary exercise testing in the clinical and prognostic assessment of diastolic heart failure.

OBJECTIVES: This study sought to define the relative prognostic value of cardiopulmonary exercise testing (CPET) variables in heart failure (HF) patients with preserved versus reduced systolic function. BACKGROUND: Cardiopulmonary exercise testing has an established role in the assessment of patients with systolic heart failure (SHF). Two variables, peak Vo2 and, more recently, the VE/VCO2 slope, have been shown to be extremely valuable in risk stratification. However, data are lacking in terms of the prognostic value of CPET in patients with diastolic heart failure (DHF). METHODS: A total of 409 HF patients underwent CPET. Patients were divided into three groups according to the following left ventricular ejection fraction (LVEF) cutoffs: > or =40%, > or =45%, and > or =50%. The CPET response and the ability of peak VO2 and the VE/VCO2 slope to predict total mortality and hospitalization were examined. RESULTS: At univariate Cox regression analysis, both the peak VO2 and the VE/VCO2 slope were significant predictors in SHF and DHF. Multivariate analysis documented a similar prognostic power of VE/VCO2 slope and peak VO2 in all SHF groups. Conversely, in DHF patients, VE/VCO2 slope outnumbered peak VO2, remaining the only predictor regardless of LVEF. In DHF, the area under the receiver operating characteristic curve for the VE/VCO2slope identified a cutoff of 32.6 (74% sensitivity, 52% specificity), 33.1 (76% sensitivity, 62% specificity), and 33.3 (97% sensitivity, 40% specificity) for an LVEF cutoff of > or =40%, > or =45%, and > or =50%, respectively. CONCLUSIONS: These results extend the clinical and prognostic applicability of CPET to DHF. An impairment in exercise ventilation rather than peak VO2 holds clinical and prognostic impact in this increasing subset of patients.

Diastole↗

What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography?

OBJECTIVES: The objective was to determine the prognostic value of rubidium-82 (82Rb) positron emission tomography (PET) myocardial perfusion imaging (MPI). BACKGROUND: 82Rb PET MPI accurately diagnoses coronary artery disease (CAD). However, there are limited data evaluating its prognostic value. METHODS: Follow-up (3.1 +/- 0.9 years) was obtained in 367 patients who underwent dipyridamole 82Rb PET MPI. Patients were divided into groups based on their summed stress score (SSS): group I, normal (<4); group II, mild (4 to 7); and group III, moderate (8 to 11) to severe (> or =12). RESULTS: There were significant differences among patients in the 3 SSS groups for hard events (cardiac death and myocardial infarction [MI]) (p < 0.001) and total cardiac events (hard events, revascularization and hospitalization) (p < 0.001). The annual hard events rates were 0.4%, 2.3%, and 7.0% in the normal, mild, and moderate-severe groups, respectively. In adjusted survival models, 82Rb PET SSS was the strongest predictor of total cardiac events and a significant predictor of hard events. Among patients referred for PET after 99mTc single-photon emission computed tomography, the annual total event rate was higher with abnormal versus normal SSS on PET (15.2% vs. 1.3%, p < 0.001). In patients with obesity, the annual total event rate was 11.1% with an abnormal scan and 1.5% with a normal scan (p < 0.001). CONCLUSIONS: This study shows that 82Rb PET MPI has significant prognostic value for predicting cardiac events, including death and MI. It also seems to have prognostic value in patients whose diagnosis remains uncertain after single-photon emission computed tomography MPI and in obese patients. The prognostic value of PET MPI may improve the management of cardiac patients.

Aged↗

Endogenous immune response to early- and intermediate-stage melanoma is correlated with outcomes and is independent of locoregional relapse and standard prognostic factors.

BACKGROUND: Standard prognostic factors, including precise staging of the regional lymph nodes, cannot accurately determine which early-stage melanomas will metastasize. The immune response to a 90-kd tumor-associated antigen correlates with occult nodal disease and survival of patients receiving vaccine therapy for melanoma. We hypothesized that this response might have prognostic significance independent of standard prognostic features. STUDY DESIGN: Patients with primary melanomas 1.01 to 2.00 mm and tumor-negative regional lymph nodes were identified. Group 1 comprised 50 patients who died of metastases within 7 years after complete surgical treatment; group 2 comprised 50 patients who were matched with group 1 for six standard prognostic features but who lived at least 10 years without recurrence. Postoperative sera were analyzed for an immune complex to TA90 and for immunoglobulin-G and immunoglobulin-M antibodies against TA90. RESULTS: Median thickness of the primary melanoma was 1.40 +/- 0.31 mm and 1.42 +/- 0.32 mm in groups 1 and 2, respectively; median Clark's level of invasion was III in both groups, and 26 patients in each group had ulcerated primaries. Median TA90-IC level and rate of TA90-IC positivity (optical density greater than 0.410) were 0.557 +/- 0.43 and 82%, respectively, in group 1 and 0.305 +/- 0.15 and 18%, respectively, in group 2 (p < 0.001). The anti-TA90 IgM level was significantly elevated in 12% of group 1 (median titer 1:150) and 62% of group 2 (median titer 1:800) (p < 0.001). There was no significant difference in anti-TA90 IgG levels between the two groups. CONCLUSIONS: A positive TA90-IC level and absence of an anti-TA90 IgM response correlate with distant metastasis when melanoma is low risk or intermediate risk by standard prognostic factors.

Adult↗

The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available?

BACKGROUND/AIMS: Prognosis assessment in patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Okuda classification, but new staging systems (Cancer of the Liver Italian Program score, Chinese University Prognostic Index, French classification and Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We investigated the value of known prognostic systems in the particular setting of a surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated with radical therapies (resection and percutaneous ablation). METHODS: A retrospective analysis of 187 HCCs observed at a single Institution from 1990 and 1999 was performed. By using survival time as the only outcome measure (Kaplan-Meier method and Cox regression), the performance of any prognostic system was assessed according the criteria of discriminatory and stratification abilities between different stages, homogeneity of survival within each stage and additional explanatory power respect to the other classifications. RESULTS: In the particular cohort studied, BCLC proved the best HCC prognostic system. This was true for the whole study group and for the 2 subgroups of surgical and non-surgical patients. CONCLUSIONS: BCLC staging showed the best interpretation of the survival distribution in an HCC population comprising a large proportion of tumors treated with potentially radical therapies.

Adult↗